(Project 5, Janmey) Unlike other elements of the cytoskeleton, individual IFs and the networks they form can withstand large deformations that would rupture F-actin or microtubules The molecular mechanisms that control vimentin IF assembly in the cell and that link IFs together so that they form mechanically resistant networks are also not well understood. Specific crosslinking proteins do not appear to be required for network formation, and several bonds between IF subunit C-terminal extensions and the sides of other filaments have been reported. Complementary attractive interactions between vimentin IFs mediated by multivalent cations are also important. Identifying the molecular mechanisms for IF crosslinking and bundle formation remains a major challenge to defining this system with the same detail as currently available for network formation by other biopolymers. This project will define the mechanism that control vimentin polymerization and network formation in the cytoplasm, and quantify how network of purified vimentin Ifs and vimentin containing cells and cytoskeletons respond to large amplitude compressive strains that occur in vivo. The project will collaborate with other project of this PPG in both cell biologic and biophysical studies and engage the PPG animal core to produce mice and tissues with altered vimentin expression to determine the role of vimentin on tissue mechanics and responses of genetically modified mice with altered vimentin to mechanical stresses.
| Wu, Pei-Hsun; Aroush, Dikla Raz-Ben; Asnacios, Atef et al. (2018) A comparison of methods to assess cell mechanical properties. Nat Methods 15:491-498 |
| Robert, Amélie; Tian, Peirun; Adam, Stephen A et al. (2018) Kinesin-dependent transport of keratin filaments: a unified mechanism for intermediate filament transport. FASEB J :fj201800604R |
| Li, Wen; Zhang, Liyuan; Ge, Xuehui et al. (2018) Microfluidic fabrication of microparticles for biomedical applications. Chem Soc Rev 47:5646-5683 |
| Wang, Zheng; Divanyan, Alex; Jourd'heuil, Frances L et al. (2018) Vimentin expression is required for the development of EMT-related renal fibrosis following unilateral ureteral obstruction in mice. Am J Physiol Renal Physiol 315:F769-F780 |
| Wang, Liqun; Xia, Jing; Li, Jonathan et al. (2018) Tissue and cellular rigidity and mechanosensitive signaling activation in Alexander disease. Nat Commun 9:1899 |
| Bucki, Robert; Durna?, Bonita; W?tek, Marzena et al. (2018) Targeting polyelectrolyte networks in purulent body fluids to modulate bactericidal properties of some antibiotics. Infect Drug Resist 11:77-86 |
| Guo, Ming; Pegoraro, Adrian F; Mao, Angelo et al. (2017) Cell volume change through water efflux impacts cell stiffness and stem cell fate. Proc Natl Acad Sci U S A 114:E8618-E8627 |
| Prakadan, Sanjay M; Shalek, Alex K; Weitz, David A (2017) Scaling by shrinking: empowering single-cell 'omics' with microfluidic devices. Nat Rev Genet 18:345-361 |
| Costigliola, Nancy; Ding, Liya; Burckhardt, Christoph J et al. (2017) Vimentin fibers orient traction stress. Proc Natl Acad Sci U S A 114:5195-5200 |
| Zaritsky, Assaf; Obolski, Uri; Gan, Zhuo et al. (2017) Decoupling global biases and local interactions between cell biological variables. Elife 6: |
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